Quantitative method for the therapeutic treatment of sleep disorders

ABSTRACT

The present invention relates to a method of analyzing a subject for excessive daytime sleepiness, and more particularly to a quick (short duration), quantitative method of sleep disorder analysis. The present invention additionally relates to a method, which can be used to quantitatively measure the treatment endpoints for the subject, i.e., appropriate levels of stimulants. Additionally, the present invention relates to a device for sleep disorder analysis.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.10/454,156, filed Jun. 4, 2003, issued as U.S. Pat. No. 6,993,380 B1 onJan. 31, 2006.

The U.S. Government has a paid-up license in this invention and theright in limited circumstances to require the patent owner to licenseothers on reasonable terms provided for by the terms of grant numbers 5R44 HL70327-03 and N43-NS-9-2307 awarded by the National Institutes ofHealth.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a method of analyzing a subject forexcessive daytime sleepiness, and more particularly to a quick (shortduration), quantitative method of sleep disorder analysis. The presentinvention additionally relates to a method, which can be used toquantitatively measure the treatment endpoints for the subject, i.e.,appropriate levels of stimulants.

2. Technical Background

Nearly one in seven people in the United States suffer from some type ofchronic sleep disorder, and only fifty percent (50%) of people areestimated to get the recommended seven (7) to eight (8) hours of sleepeach night. It is further estimated that sleep deprivation and itsassociated medical and social costs (loss of productivity, industrialaccidents, etc) exceed $150 billion dollars per year. Excessivesleepiness can deteriorate the quality of life and is a major cause ofmorbidity and mortality due to its role in industrial and transportationaccidents. Sleepiness further has undesirable effects on motor vehicledriving, employment, higher earning and job promotion opportunities,education, recreation, and personal life.

Excessive daytime sleepiness (EDS) is a symptom describing an increasedpropensity to fall asleep, often during monotonous or sedentaryactivities. Though sometimes difficult, EDS vs. fatigue need to bedifferentiated. Fatigue or lethargy is where a subject senses a lack ofenergy or physical weakness and may not have an increased propensity tofall asleep at an inappropriate time. The underlying etiology of EDSgenerally falls into three categories: chronic sleep deprivation,circadian disorders (shift work), and sleep disorders. EDS is currentlydiagnosed via two general methods. The first is via subjective methodssuch as the Epworth and Standford Sleepiness Scale, which generallyinvolves questionnaires where the patients answer a series ofqualitative questions regarding their sleepiness during the day. Withthese methods, however, it is found that the patients usuallyunderestimate their level of sleepiness or they deliberately falsifytheir responses because of their concern regarding punitive action, oras an effort to obtain restricted stimulant medication.

The second is via physiological-based evaluations such as all-nightpolysomnography to evaluate the patients patient's sleep architecture(e.g., obtaining respiratory disturbance index to diagnose sleep apnea)followed by an all-day test such as the Multiple Sleep Latency Test(MSLT) or its modified version, Maintenance of Wakefulness Test (MWT).The MSLT consists of four (4) to five (5) naps and is considered themost reliable objective measure of sleepiness to date. The MSLT involvesmonitoring the patient during twenty (20) to forty (40) minute napperiods in two-hour intervals one and one half hour (1.5 hrs) to threehours (3 hrs) after awakenings to examine the sleep latency and thesleep stage that the patient achieves during these naps, i.e., the timeit takes for the patient to fall asleep. A sleep disorder such asnarcolepsy for example is diagnosed when the patient has a restful nightsleep the night before but undergoes rapid eye movement sleep (REMsleep) within five (5) minutes of the MSLT naps. The MWT is a variationof the MSLT. The MWT provides an objective measure of the ability of anindividual to stay awake.

While the MSLT and MWT are more objective and therefore don't have thesame limitations as mentioned for the subjective tests, the MSLT and MWThave their own limitations. Both the MSLT and MWT require an all-daystay at a specialized sleep clinic and involve monitoring a number ofnap opportunities at two hour intervals throughout the day. Further, theMSLT mean sleep latency is only meaningful if it is extremely short induration (e.g., to diagnose narcolepsy), and only if the overnightpolysomnogram does not show any sleep disordered breathing. Anotherproblem with the MSLT mean sleep latency is the so-called “floor effect”where the sleep latency in the pathologically sleepy patients can bealmost zero (0) minutes, i.e., the patient falls asleep almostimmediately following turning off the light in the MSLT test. This typeof result has a tendency to limit the diagnostic resolution of the test.Finally, studies have shown that the MSLT is not particularly suited forgauging the effects of therapeutic intervention. This was demonstratedin studies by Thorpy in 1992 and Van den Hoed et al. in 1981 showing noreliable reduction in sleepiness in patients given stimulant medicationsfor narcolepsy.

The MWT was developed in 1982, in part to address some of theshortcomings of the MSLT method. The MWT eliminated the “floor effect”in the MSLT test shown in narcoleptic patients due to the instruction inthe MWT test to the patient to stay awake. The MWT, however, createdanother problem at the other end of the sleep latency period called the“ceiling effect”. The “ceiling effect” is the tendency of less “sleepy”individuals to perform the MWT without falling asleep. In fact, thelength of the MWT trial was lengthened from twenty (20) to forty (40)minutes in 1984 because it was observed that patients with histories ofexcessive daytime sleepiness were too often able to maintain wakefulnessfor the twenty (20) minutes. In addition, while the MSLT and MWT areobjective and “broadly” quantitative tests in that they both require thepatient to fall asleep during the test and they measure the number ofthose incidents of sleep during the testing regiment, these tests aretoo costly and lack the degree of quantitative resolution necessary toeasily permit measurement of effects of therapeutic intervention anddegrees.

In recent years there have been a number of efforts to develop systemsfor detecting alertness and drowsiness by attempting to quantify thebrain waves of a subject. Most of these systems have been aimed at thealertness monitoring field for alertness critical applications. Examplesof these types of systems are as follows: Levin U.S. Pat. No. 6,167,298discloses a device for monitoring and maintaining an alert state ofconsciousness for a subject wearing the device. With this device analert mental state is maintained through monitoring of brain wavepatterns to detect if a transition from an alert to a non-alert mentalstate is about to occur, or has occurred. If so, the device provides astimulus until such time as an alert mental state, as assessed by thebrain wave activity, is restored. Levendowski et al. U.S. Pat. No.6,496,724 discloses a method of classifying individualelectroencephalogram (EEG) patterns along an alertness-drowsinessclassification continuum. The results of the multi-level classificationsystem are applied in real time to provide feedback to the user via anaudio or visual alarm, or are recorded for subsequent off-line analysis.Kaplan et al. U.S. Pat. No. 5,813,993 discloses an alertness anddrowsiness detection and tracking system. The system claims improvedperformance by preserving and analyzing brain wave signal components atfrequencies above 30 Hz.

Most of the methods, systems or devices currently on the market eitherprovide a qualitative means for analyzing for excessive daytimesleepness or more specifically for sleep disorders, or asemi-quantitative means for classifying a subjects state of alertness.None of the above mentioned methods, systems or devices provide aquantitative means of measuring and determining whether an individualsuffers from excessive daytime sleepiness and more specifically from asleeping disorder, particularly one in which the analysis andmeasurement are capable of being provided in a short time duration andat low cost to the patient or insurance company. It is therefore anobject of the present invention to provide a quantitative method ofanalysis wherein it can be determined whether a patient exhibitsexcessive daytime sleepiness based on a number or a quantitative profileof the patient exceeding a predetermined number or quantitative profilerespectively over a given period of time. It is still another object ofthe present invention that this method be inexpensive and/or of shorttime duration. It is still another object of the present invention thata patient's therapeutic treatment can be more accurately determinedbased on the quantitative number or profile from the testing of thepatient, and can subsequently be adjusted accordingly based on asubsequent test of the patient.

SUMMARY OF THE INVENTION

The present invention relates to a method of analyzing a subject forexcessive daytime sleepiness, and more particularly to a quick (shortduration), quantitative method of sleep disorder analysis. The presentinvention additionally relates to a method, which can be used toquantitatively measure the treatment endpoints for the subject'sexcessive daytime sleepiness, i.e., appropriate levels of stimulants.

There are numerous embodiments of the present invention, which areenvisioned with a few of those listed below. The present inventionrelates to a method of analyzing a subject, and preferably a humansubject for excessive daytime sleepiness and more preferably forsleeping disorders. These sleep disorders include but are not limited tonarcolepsy, respiratory sleep disorders including obstructive sleepapnea, periodic limb movement disorder, restless leg syndrome, substanceinduced sleep disorders, dyssomnias, parasomnias, and sleep disordersrelated to a medical condition.

The method of sleep analysis of the present invention is generally andpreferably of a short duration. This method represents a major costsavings for patients and their insurance company(s), and a major timesavings for the patient and physician. This method can be used either asa screening test for sleep disorders, or as it gains more acceptability,as the primary method of diagnosing sleep disorders. Since this methodis a quantitative one, the method allows the physician or trainedtechnician to more easily determine the degree or level of the subject'sdisorder, and likewise provides another method of assessing theimprovement of the subject after treatment or therapy, i.e., eitherphysically or through medication.

The present invention further is related to a system used for theanalysis. The system is potentially inexpensive and portable allowingfor more extensive screening of the public for these types of disorders.This system could be used in a physician's office, or directly at thepatient's home by the physician or trained technician.

In one embodiment, the present invention includes a method of analyzinga subject for sleep disorders over a test time period comprising thesteps of determining that a subject has maintained a normal sleepingpattern prior to the analysis; using at least one sensor to measure thesubject's brain wave signals over a measurement time period, themeasurement time period comprising a number of time segments; analyzingthe subject's brain wave signals to estimate or determine a number or apower spectrum profile for each time segment; and making a determinationthat the subject has a sleep disorder based in part on a computed numberbased on the number for each time segment over the measurement timeperiod exceeding a predetermined threshold number, a profile of thenumbers over the measurement time period exceeding a predeterminedthreshold profile over the time period, or the power spectrum profileexceeding a predetermined threshold power spectrum profile over themeasurement time period. Optionally, this embodiment further includesthe method wherein the subject's brain wave signals is transformed to apower spectrum, the power spectrum comprising an alpha component and oneor more sub-alpha components, the subject's brain wave signals areanalyzed to determine a ratio of the one or more sub-alpha components tothe alpha component of the power spectrum, and the determination ofwhether the subject has a sleep disorder is based in part on an averageof the ratio of the one or more sub-alpha components to the alphacomponent exceeding a predetermined threshold number or thresholdprofile over the measurement time period.

In another embodiment, the present invention includes a method ofanalyzing a subject for excessive daytime sleepiness over a test timeperiod comprising the steps of using at least one sensor to measure asubject's brain wave signals over a measurement time period, themeasurement time period comprising a number of time segments; analyzingthe subject's brain wave signals to estimate or determine a powerspectrum profile for each time segment of the measurement time period,the power spectrum comprising a alpha component and at least onesub-alpha component, and from these components a ratio of the one ormore sub-alpha components to the alpha components for each time segment;and making a determination of the degree of excessive daytime sleepinessbased in part on the ratio over the measurement time period.

In still another embodiment, the present invention includes a method ofanalyzing a subject for excessive daytime sleepiness over a test timeperiod comprising the steps of using at least one sensor to measure asubject's brain wave signals over a measurement time period, themeasurement time period comprising a number of time segments; analyzingthe subject's brain wave signals to estimate or determine a number fromthe power spectrum of the brain wave signals in the from about 0 toabout 30 Hz range or a power spectrum profile from the signal componentsfrom the brain wave signals in the from about 0 to about 30 Hz range foreach time segment; and making a determination of the degree of excessivedaytime sleepiness based in part on the number or the power spectrumprofile for the time segments over the measurement time period whereinthe measurement time period begins at least about 2 minutes after thetest time period beings and wherein the test time period is less thanabout 60 minutes.

In still another embodiment, the present invention includes a method ofanalyzing a subject for sleep disorders comprising the steps of placingat least one sensor onto a subject's head having a brain wave signal;providing a stimulus to the subject; measuring the subject's response tothe stimulus and the brain wave signal through the sensor; analyzing thebrain wave signal; and making a determination that the subject has asleep disorder based in part on the brain wave signal analysis over ameasurement time period, and in part on the subject's response to thestimulus over a period of time.

In still another embodiment, the present invention includes a method oftherapeutically treating a subject for sleep disorders comprising thesteps of quantitatively analyzing a subjects brain wave signals andusing the quantitative analysis in estimating or determining whether thesubject has a sleeping disorder; making a physical change to the subjector giving the subject a medication to make an improvement to thesubject's sleeping disorder based in part on the quantitative analysis;quantitatively analyzing a second time the subjects brain wave signalsto estimate or determine the extent of the improvement to the subject'ssleeping disorder; and, if necessary, making an additional physicalchange to the subject or reducing or increasing the medication inresponse to the previous step.

In still yet another embodiment, the present invention includes a systemfor analyzing sleep disorders of a subject comprising at least one brainwave sensor that measures brain wave signals; a component for deliveringa stimulus to a subject; a component for response by the subject to thedelivered stimulus; a processor or computer that analyzes the measuredbrain wave signals in relation to the stimulus to and response from thesubject to determine whether the subject suffers from a sleepingdisorder.

Additional features and advantages of the invention will be set forth inthe detailed description which follows, and in part will be readilyapparent to those skilled in the art from that description or recognizedby practicing the invention as described herein, including the detaileddescription which follows, the claims, as well as the appended drawings.

It is to be understood that both the foregoing general description andthe following detailed description are merely exemplary of theinvention, and are intended to provide an overview or framework forunderstanding the nature and character of the invention as it isclaimed. The accompanying drawings are included to provide a furtherunderstanding of the invention, and are incorporated in and constitute apart of this specification. The drawings illustrate various embodimentsof the invention, and together with the description serve to explain theprinciples and operation of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. is an illustration of a subject wearing a sensor to pickup andtransmit brain wave signals to a computer for quantitatively analyzingthe subject for excessive daytime sleepiness and/or sleep disorders.

FIG. 2. is a graph showing a comparison of a number of subjects'profiles with a threshold profile to determine whether the subjectssuffer from a sleeping disorder.

FIG. 3. is another graph showing a comparison of the a number ofsubjects' cumulative profiles with a threshold cumulative profile todetermine whether the subjects suffer from a sleeping disorder.

DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention relates to a method of analyzing a subject forexcessive daytime sleepiness, and more particularly to a quick (shortduration), quantitative method of sleep disorder analysis. The presentinvention also includes a sleep analysis system.

Various embodiments of the present invention include a step fordetermining whether the subject being analyzed for a sleep disordermaintained a normal sleeping pattern prior to the analysis. This stepcan be performed or accomplished a number of ways. In the simplest form,the subject can be questioned regarding his or her previous sleeppatterns. In a somewhat more complex form the subject can be requestedto fill out a questionnaire, which then can be graded to determinewhether his or her previous sleep patterns where normal (or appearednormal). In an even more complex form the subject might undergo allnight polysomnography to evaluate the subject's sleep architecture(e.g., obtaining respiratory disturbance index to diagnose sleep apnea).One of the objectives of this step is to ensure that the quantitativedata results of the subject's brain wave analysis are not the result ofor affected by the subject's previous environmental factors i.e.,intentional lack of sleep, etc. It is clear that there are numerous waysbeyond those examples previously mentioned of determining whether thesubject being analyzed maintained or thought they were maintaining anormal sleeping pattern prior to analysis, therefore the examples givenabove are included as exemplary rather than as a limitation, and thoseways of determining whether the subject maintained or thought they weremaintaining a normal sleeping pattern known to those skilled in the artare considered to be included in the present invention.

The present invention involves the step of using at least one sensor tomeasure a subject's brain wave signals over a period of time. The brainwave or electroencephalogram (EEG) signals can be obtained by any methodknown in the art, or subsequently developed by those skilled in the artto detect these types of signals. Sensors include but are not limited toelectrodes or magnetic sensors. Since brain wave signals are, ingeneral, electrical currents which produce associated magnetic fields,the present invention further anticipates methods of sensing thosemagnetic fields to acquire brain wave signals similar to those which canbe obtained through for example an electrode applied to the subjectsscalp. The subject(s) referred to in the present invention can be anyform of animal. Preferably the subject(s) are mammal, and mostpreferably human.

If electrodes are used to pick up the brain wave signals, theseelectrodes may be placed at one or several locations on the subject(s)'scalp or body. The electrode(s) can be placed at various locations onthe subject(s) scalp in order to detect EEG or brain wave signals.Common locations for the electrodes include frontal (F), parietal (P),anterior (A), central (C) and occipital (O). Preferably for the presentinvention at least one electrode is placed in the occipital position. Inorder to obtain a good EEG or brain wave signal it is desirable to havelow impedances for the electrodes. Typical EEG electrodes connectionsmay have an impedance in the range of from 5 to 10 K ohms. It is ingeneral desirable to reduce such impedance levels to below 2 K ohms.Therefore a conductive paste or gel may be applied to the electrode tocreate a connection with an impedance below 2 K ohms. Alternatively, thesubject(s) skin may be mechanically abraded, the electrode may beamplified or a dry electrode may be used. Dry physiological recordingelectrodes of the type described in U.S. patent application Ser. No.09/949,055 are herein incorporated by reference. Dry electrodes providethe advantage that there is no gel to dry out, no skin to abrade orclean, and that the electrode can be applied in hairy areas such as thescalp. Additionally if electrodes are used as the sensor(s), preferablyat least two electrodes are used—one signal electrode and one referenceelectrode; and if further EEG or brain wave signal channels are desiredthe number of electrodes required will depend on whether separatereference electrodes or a single reference electrode is used. For thevarious embodiments of the present invention, preferably an electrode isused and the placement of at least one of the electrodes is at or nearthe occipital lobe of the subject's scalp.

Now referring to FIG. 1, which is an illustration of a subject wearing asensor to pick up and transmit brain wave signals to a computer forquantitatively analyzing the subject for excessive daytime sleepinessand/or sleep disorders. In FIG. 1 an electrode (sensor) 10 is placed onthe central lobe 12 of the subject's scalp 14, and another referenceelectrode (sensor) 10 is placed behind the subject's ear 15. Theelectrodes 10 are dry electrodes. The electrodes 10 are releasablyconnected to leads 16 which can be connected to a processing unit (notshown) or to a wireless telemetry unit 18, which transmits the raw brainwave or EEG signal to a receiver 19 and then processing unit 20 foranalysis. Not shown, it is clear to someone skilled in the art where theplacement of the electrode 10 will be required in order to maintain aclose proximity between the electrode 10 and that portion of the brain.The number of electrodes 10 and likewise signals to be analyzed dependson the environment in which the sleep analysis system is to be used. Ina more formal setting, it may be desirable to collect and analyzemultiple brain wave or EEG signals from several locations on a subject'sscalp. In a less formal setting such as a family practitioner's,internist's or general practitioner's office, it may be desirable toapply one sensor that requires little or no expertise in placement ofthe electrode, i.e., a dry electrode. The electrodes can preferably beplaced in the locations of the frontal (F), parietal (P), anterior (A),central (C) and occipital (0) lobes of the brain.

Once the sensor(s) is in place relative to the subjects head in order todetect the subject's brain wave or EEG signal, the subject is preferablyinstructed to sit in a comfortable chair or lie down in a supineposition. Further preferably, the subject is instructed to close theireyes throughout the test and relax, but to try and not fall asleep. Thesubject's brain wave or EEG signals are preferably recorded and analyzedduring a test time period. The test time period is defined as the periodof time in which the subject's brain waves signals are measured orrecorded, and in general this corresponds closely to the time period inwhich the subject is hooked up to the quantitative, excessive daytimesleepiness measuring system. Generally, the test time period ispreferably less than about 4 hours, more preferably less than about 2hours, still more preferably less than about 60 minutes, still morepreferably less than about 30 minutes, even still more preferably lessthan about 20 minutes, even still more preferably less than 15 minutes,and most preferably less than about 10 minutes. It has been found,generally, that a given amount of test time is necessary for a subject'sbrain wave signals to evolve into a consistent pattern. Therefore, theperiod of time in which brain waves are used for analysis preferablybegins after this initial period of inconsistent data and is called themeasurement time period. Preferably the measurement time period (alsoknown as the time period over which the data is analyzed) begins atleast 2 minutes after the test time period began, more preferably 4minutes after the test time period began and most preferably 6 minutesafter the test time period began. The measurement time period endsbefore or at the time the test time period ends.

Optionally the test may include the subject's response to one or moretypes of stimulus. Still further preferably, if this step is includedinto the method, the subject is instructed to respond to certain typesof the one or more stimulus. Still further preferably, the subject'sresponse and lack of response are measured along with the timing of thesubjects response relative to the stimulus. The stimulus provided to thesubject can be based on any of the subject's senses including hearing,sight, smell, touch, or taste. Preferably, because the subject may berequested to close their eyes during the test (and given the types ofstimuli devices currently readily available) the stimulus is based onthe subject's sense of hearing or touch. More preferably, the stimulusis based on the subject's sense of hearing. In one particular embodimentof the subject's sensory response, a processor, such as a PC computerwith specialized software, is used to generate a series of auditorytones for the subject. These auditory tones are further linked to thebrain wave or EEG signals of the subject. With respect to the auditorytones, the subject could be instructed to listen for a particular tone(and respond in some way) and ignore the other tones. An example of thiswould be to generate a series of auditory tones in the form of phonemessuch as “BA” or “GI”. The volume level would be set low enough such thatthe subject would be able to comfortably hear the tone but not too loudto disturb or startle. These tones can be communicated to the subjecteither through ear phones or speakers. These tones would be generated bya program or software on a computer or processor respectively. For theduration of the test, the subjects would be instructed to listen for aparticular tone and ignore other tones. Preferably, the tones are atleast 1.5 seconds apart. In the preferred protocol, the subject willhave to press a switch (e.g., a push-button) as soon as they hear aparticular tone (e.g., BA) and ignore other types of tones (GI). Forembodiments of the present invention, where the protocols involvepressing a push-button or other types of switches, preferably thesubject practices a few times before the start of the test to becomefamiliar with the feel and the handling of the switch. If the subject isunable or unwilling to press the switch, protocols can be used that donot require such a manual response.

During the test, the subject's response to the stimulus is preferablymeasured and the accuracy of the subject's response is evaluatedpreferably by a computer or processor by examining the status of thesubject's response (through for example the switch identified in the oneembodiment) following the onset of the stimulus (for example theauditory tones in the same embodiment). In the particular embodimentreferred to the processor or computer would compute the time delaybetween the occurrence of the auditory stimulus and the time in whichthe switch is activated. If the subject manages to press the switchwithin the allowable interval immediately after the appropriate auditorystimulus (i.e., the tone for which the subject is instructed torespond), the analysis through the processor or computer assigns acorrect response for that duration of the test. If, however, on theother hand the subject fails to respond or activates the switch when thestimulus was supposed to be ignored, the processor or computer assignsan incorrect response for that duration of the test. Preferably, thesubject's reaction time and/or accuracy of response are used (in part)along with the analysis of the subject's brain waves to make adetermination of whether the subject is suffering from a sleepingdisorder. Furthermore, the subject's measured response can be used as anindicator as to whether the subject is cooperating with the test bycomparing the measured response with the analyzed brain wave signalsover the same time period.

During the testing of a subject for excessive daytime sleepiness or fora sleep disorder, preferably, the subject's brain wave or EEG signalsare collected and analyzed to estimate or determine a number or powerspectrum profile for each sampling moment or time segment. The signalscan be collected through conventional recorders, analog signalprocessors or similar other devices and analyze after collection,however, given the easy access to digital technology such as processorsand computers preferably the collection and analysis of the brain waveor EEG signals is carried out nearly concurrently (or simultaneously)using these digital means. In one embodiment of the present invention, aprocessor or computer receives digitized signals based on analog signalsfrom the sensor used to measure the subject's brain wave or EEG signals.The sampled brain wave or EEG signals are then band-pass filtered inpreferably the 0.1 Hz to 50 Hz range using a digital filter, e.g. abutterworth filter. This is followed by a first step of artifactdetection and removal.

In the first step of analysis after data collection, the artifacts inthe data are preferably identified and removed. In artifact detectionand removal, the band-pass filtered data of the brain wave or EEG sampleis compared with the standard deviation of the brain wave or EEG sampleover the entire test or a portion of the test in which that sample istaken. If the brain wave or EEG sample is greater than some multiple ofthe standard deviation, preferably greater than about 3 times and morepreferably greater than about 5 times, then that EEG sample is marked asan artifact and is replaced by a value that is derived from theartifact-free segment of the data immediately before. The artifact-freesegment of data is that portion of the sampling data preferably greaterthan about 0.1 seconds before and also preferably less than about 0.6before the artifact in sampling time.

This brain wave or EEG sample data is then preferably broken intoconsecutive sampling moments or time segments. These sampling moments ortime segments are preferably 2 seconds in duration allowing for example400 sampling points if the brain wave or EEG signal sampling rate was200 samples per second. Each consecutive time segment is thentransformed into a frequency domain representation (also known as powerspectrum or frequency power spectrum) using techniques known to thoseskilled in the art. One technique, which is preferred, is to use astandard Fast Fourier Transform method (FFT). The FFT coefficientsobtained are then squared and scaled to obtain the power spectrum plot(i.e., the power of brain wave or EEG signal at each frequency level).In this embodiment since the segment duration is for 2 seconds, thefrequency resolution will be 0.5 Hz, and power values can be obtainedfor frequency bins of 0.5, 1, 1.5, 2, 2.5, . . . , 50 Hz.

The power spectrum of each time segment is used to determine if the timesegment contains movements and other types of artifacts. Some of theartifacts manifest themselves in abnormally large power values in allfrequencies, particularly at very low frequencies <10 Hz, compared tothe power spectrum of the entire study. Upon detection of suchabnormally high power spectra, preferably the entire sampling segment(in this embodiment 2 seconds) is marked as contaminated by theartifacts and is replaced by an average power spectrum of theartifact-free segments.

Brain wave data that is monitored and analyzed according to the presentinvention is between about 0.1 to about 50 Hz. Preferably, between 0.1to about 30 Hz, more preferably between about 0.1 to about 15 Hz, andmost preferably between about 0.1 to about 13 Hz. Also in certainembodiments of the present invention brain waves are categorized asdelta, theta, alpha and beta waves or components. Delta waves orcomponents generally exhibit brain wave or EEG activity in the frequencyrange from about 1 Hz to about 4 Hz, theta waves or components generallyin the frequency range from about 6 Hz to about 7.5 Hz, alpha waves orcomponents generally in the frequency range from about 7.5 Hz to about13 Hz, and beta waves or components generally in the frequency rangefrom about 13 Hz to about 30 Hz. As those skilled in the art willappreciate, the boundaries between these components are somewhatarbitrary. Thus, the foregoing delineations are intended to be exemplaryand not limiting. Furthermore, use of other components, whether nowknown or later discovered, are within the scope of the invention.

In one embodiment of the present invention, the frequency power spectrumor power spectrum is used to determine a number for each sampling momentor time segment, and an average number over a measurement time period,which may include numerous sampling moments or time segments isdetermined. This number is then compared with a predetermined thresholdnumber which has been calculated (and in a sense calibrated) based onprevious tests using this technique on individuals with no knownsleeping disorders, and individuals with a range of known sleepingdisorders. In a more specific embodiment, a number is obtained by usingonly the frequency power spectrum or power spectrum data at frequenciesbelow about 13 Hz. In this embodiment, data at frequencies below about13 Hz is subjected to some form of mathematical manipulation such asbeing input into an algorithm. As those skilled in the art willappreciate, the weighting of data from the various frequency powerspectrums or power spectrum may vary as well as the number of powerspectrum frequencies or power spectrum used in order to magnify thequantitative resolution of this method. In an even more specificembodiment of this sleep analysis method, a number is obtained at leastin part based upon the sum of the power in the 0.5-7.5 Hz frequency (andeven more preferably in the 4-7.5 Hz frequency) bands divided by the sumof the power in the 7.5-13 Hz frequency bands (and more preferably inthe 7.5-9.5 Hz frequency bands) to determine a ratio or an averagenumber over a given measurement time period or period of time. Thisnumber is then compared with a predetermined threshold number which hasbeen calculated (and in a sense calibrated) based on previous testsusing this even more specific technique on individuals with no knownsleeping disorders, and individuals with a range of known sleepingdisorders.

In another embodiment of the present invention, the frequency powerspectrum or power spectrum is used to determine a profile of thesubjects a sampling data over a period of time or measurement timeperiod. The period of time or measurement time period for the profilemay either be the entire testing period, some portion thereof, which mayinclude numerous sampling moments or time segments. This profile is thencompared with a predetermined threshold profile which has beendetermined based on previous tests using this technique on individualswith no known sleeping disorders, and individuals with a range of knownsleeping disorders (or based on what is determined to be a typicalprofile for someone with no known sleeping disorder or for an individualwith a specific sleeping disorder). In another more specific embodiment,a profile is obtained by using only the frequency power spectrum orpower spectrum data at frequencies below about 13 Hz. In this morespecific embodiment, data at frequencies below about 13 Hz is subjectedto some form of mathematical manipulation such as being input into analgorithm to form the profile. As those skilled in the art willappreciate, the weighting of data from the various power spectrumfrequencies may vary as well as the number of power spectrum frequenciesor power spectrum used. In an even more specific embodiment of thissleep analysis method, a profile is obtained over a period of time equalto all or part of the test that at least in part based upon the sum ofthe power in the 0.5-7.5 Hz frequency (and even more preferably in the4-7.5 Hz frequency) bands divided by the sum of the power in the 7.5-13Hz frequency bands to determine an average number over a given period oftime or measurement time period. This frequency power spectrum or powerspectrum data is then plotted over time to create a profile for thesubject over the measurement time period. This profile is then comparedwith a predetermined profile which has been determine based on previoustests using this same even more specific technique on individuals withno known sleeping disorders, and individuals with a range of knownsleeping disorders (or based on what is determined to be a typicalprofile for someone with no known sleeping disorder or for an individualwith a specific sleeping disorder).

In addition to the above techniques, many other methods of analyzing thedata can be used to further enhance the resolution of the data betweensubjects and to eliminate any noise in the analyzed data. It isenvisioned that the present invention includes those techniques and anyother techniques know to those skilled in the art.

FIGS. 2 and 3 show the frequency power spectrum or power spectrumprofiles resulting from the measurement and analysis of a subject'sbrain wave signals over a measurement time period. The data wascollected using a number of EEG electrodes applied to a subject for themeasurement time period. The data was then analyzed with a computerprocessor to determine a number for each time segment. The measurementtime period in both of these FIGS. is the same as or very similar to thetest time period. The number for each time segment was then plotted overthe measurement time period to create a profile for the subject. Forboth of the FIGS. , it is clear that two of the profiles quantitativelyindicate that the subject has a sleeping disorder given that thesubject's profile exceeds a predetermined threshold profile over themeasurement time period (which can also be something less than the testtime period).

Although not shown, the analyzed data generated for the FIGS. can alsobe used to create a number for each time segment. The number for eachtime segment can be used by itself, or an average over the time segmentscan be used, or another number can be computed based on the number foreach time segment. This number for the subject can be used in part tocompare over the measurement time period to a predetermined thresholdnumber to determine whether the subject suffers from a sleeping disorderor excessive daytime sleepiness.

Also not shown, the power spectrum profiles for each time segment can beplotted over the measurement time period to create a profile for thesubject. This profile can then be compared with a predeterminedthreshold power spectrum profile to determine whether the subjectsuffers from a sleeping disorder or excessive daytime sleepiness.

FIG. 2 is a graph which is based on analysis of different subject'sbrain waves. In FIG. 2 a number was calculated from the subject's powerspectrum data for each time segment over the measurment time period, andis one embodiment showing a quantitative profile comparison. In FIG. 2,the sub-alpha power spectrum data were divided by the alpha powerspectrum data to give the ratio index or number referred to by they-axis. The horizontal line 100 in the graph represents the thresholdprofile where if the number based on the subject's power spectrum datafor each time segment exceeds or substantially exceeds the thresholdprofile then the subject suffers from excessive daytime sleepiness or asleeping disorder. It is clear from the graph that two of the subjects110 and 112 do not exceed this threshold profile. It is also evidentthat one of the subjects 120 which suffered from sleep apnea exceededthe profile substantially over the measurement time period, and afterapproximately 5 minutes into the measurement time period exceeded thethreshold profile. It is also clear that the other subject 130 thatsuffered from narcolepsy exceeded the threshold profile over the entiremeasurement time period.

FIG. 3 is another graph which is based on analysis of differentsubjects' brain waves. In FIG. 3, a number was calculated from eachsubject's power spectrum data for each time segment over a measurementtime period, and is another embodiment showing a quantitative profilecomparison. In FIG. 3, the sub-alpha power spectrum data were divided bythe alpha power spectrum data to give the ratio index or number and thisratio index or number was cumulatively calculated over the measurementtime period. The straight sloped line 200 in the graph represents thethreshold profile where if the number from subject's power spectrum datafor each time segment exceeds or substantially exceeds the thresholdprofile over the measurement time period, then it is determined that thesubject suffers from excessive daytime sleepiness or a sleepingdisorder. It is also evident that one of the subjects 220 which sufferedfrom sleep apnea exceeded the profile substantially over the testperiod, and after approximately 5 minutes into the measurement timeperiod exceeded the threshold profile. It is also clear that the othersubject 230 that suffered from narcolepsy exceeded the threshold profileover the entire measurement time period.

In another embodiment of the present invention, the methods describedabove are used to therapeutically treat a subject for sleepingdisorders, this being a new method unto itself. In this embodiment, thesubject's brain wave signals are quantitatively analyzed to determine ifthe subject has a sleeping disorder as described above by indexing orprofiling the subject, or by some other method that henceforth becomesknown to those skilled in the art. If the subject is found to have asleeping disorder, a physician, technician or veterinariantherapeutically treats the subject by either making a change in eitherthe physical sleeping conditions of the subject or by giving the subjecta medication to make an improvement to the subject's sleeping disorder.The subject is then re-tested by quantitatively analyzing the subject'sbrain wave signals to estimate or determine the extent of improvement ofthe subject's sleeping disorder after some reasonable period of time toallow for the therapy to have its effect. Then if based on the resultsof the re-test the subject is found to have fully improved no furthersteps are necessary. If, however, the subject is determined to have aquantitative number or profile which still varies from a normal subject(what is determined to be a quantitative number or profile for a subjectwith no sleeping disorders), a decision can be had to increase or reducethe therapeutic treatment or to add additional therapies to getalignment of the subject's quantitative number or profile with that of anormal subject. The alternating of the testing and therapeutic treatmentpossibly could have a number of iterations. It is, however, believedthat as this process is refined that a physician for example will beable to review the subject's quantitative number or profile along withother physical characteristics of the subject such as weight, etc. andvery accurately determine the type of therapeutic treatment that will benecessary, and that at this point only a small number of subject'ssubjects will need to have their therapy re-adjusted.

The present invention not only includes the above methods ofquantitatively diagnosing a subject for sleep disorders and the furthertherapeutic treatment of the subject, but also a monitor or system fordiagnosing sleep disorders. The monitor or system comprises a brain wavesensor that measures brain wave signals; a component for delivering astimulus to a subject; a component for response by the subject to thedelivered stimulus; a processor or computer that analyzes the measuredbrain wave signals in relation to the stimulus to and response from thesubject.

The sensor for the monitor or system is the same as that described foruse in the above methods. The sensor is designed to feed the brain waveor EEG signals through either leads or a wireless telemetry system intoa processor or computer.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the present inventionwithout departing from the spirit and scope of the invention. Thus, itis intended that the present invention cover the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents.

What is claimed is:
 1. A method of therapeutically treating a subjectfor sleep disorders comprising the steps of: a) determining that asubject has maintained what the subject believes sleeping pattern; b)using a processor or computer to quantitatively analyze a subject'sbrain wave signals and using the quantitative analysis in estimating ordetermining whether the subject has a sleeping disorder; c) a physician,technician or veterinarian recommending a change in the physicalsleeping conditions of the subject or giving or prescribing the subjectmedication to make an improvement to the subject's sleeping disorderbased in part on the quantitative analysis; d) using a processor orcomputer to quantitatively analyze a second time the subject's brainwave signals to estimate or determine the extent of the improvement tothe subject's sleeping disorder; and e) making an additional, change tothe physical sleeping conditions of the subject or reducing orincreasing the medication based on the extent of the improvement to thesubject's sleeping disorder estimated or determined in previous step,or, alternatively, determining that no change to the physical sleepingconditions of the subject and no reduction or increase of the medicationis necessary based on the extent of the improvement to the subject'ssleeping disorder estimated of determined, in the previous step.
 2. Themethod in claim 1, further including a step of providing one or moretypes of stimulus to the subject while the subject's brain wave signalsare collected or measured.
 3. The method in claim 2, wherein the subjectis instructed to respond after recognizing one or more of the types ofstimulus.
 4. The method in claim 3, further including the step ofmeasuring the subject's response to one or more types of stimulus andwherein the stimulus is provided on an intermittent basis.
 5. The methodin claim 1, wherein the subject brain wave signals are not reviewed by ahuman prior to the quantitative analysis.
 6. The method in claim 1,wherein the subject is given medication and the amount of medication isdecreased based on the extent of the improvement to the subject'ssleeping disorder estimated of determined by quantitatively analyzingthe subject's brain wave signals a second time.
 7. A method oftherapeutically treating a subject for sleep disorders comprising thesteps of: a) using a processor or computer to quantitatively analyze asubject's brain wave signals and using the quantitative analysis inestimating or determining whether the subject has a sleeping disorder;b) making a change in the physical sleeping conditions of the subject tomake an improvement to the subject's sleeping disorder based in part onthe quantitative analysis; and c) using a processor or computer toquantitatively analyze a second time the subject's brain wave signals toestimate or determine the extent of the improvement to the subject'ssleeping disorder; and d) making an additional change in the physicalsleeping conditions of the subject based on the extent of theimprovement to the subject's sleeping disorder estimated or determinedin the previous step, or, alternatively, determining that no change tothe physical sleeping conditions of the subject is necessary based onthe extent of the improvement to the subject's sleeping disorderestimated or determined in the previous step.
 8. The method of claim 7wherein die measurement time period is less than about 15 minutes. 9.The method of claim 7, wherein the subject's EEG is acquired using atleast one dry physiological electrode.
 10. The method of claim 7,wherein the subject's brain wave signals are not reviewed by a humanprior to the quantitative analysis.
 11. The method in claim 7, furtherincluding a step of providing one or more types of stimulus to thesubject while the subject's brain wave signals are collected ormeasured.
 12. The method in claim 11, wherein the subject is instructedrespond after recognizing one or more of the types of stimulus.
 13. Themethod in claim 12, further including the step of measuring thesubject's response to one or more types of stimulus and wherein thestimulus is provided on an intermittent basis.
 14. A method oftherapeutically treating a subject for sleep disorders comprising thesteps of: a) acquiring the subject's electroencephalogram (EEG) over ameasurement time period, the measurement time period comprising a numberof time segments, and during which measurement time period the subjectis asked to respond to one or more types of stimulus; b) using aprocessor or computer to quantitatively analyze the subject's EEG toestimate or determine a number or power spectrum profile for each of thetime segments, and using the quantitative analysis in estimating ordetermining whether the subject has sleeping-disorder by comparing thenumber or power spectrum profile with a predetermined threshold numberor profile, the predetermined threshold number or profile having beencalculated based on numbers or power spectrum profiles of individualswith no known sleeping disorders or individuals with known sleepingdisorders; c) making a change in the physical sleeping conditions of thesubject or giving the subject a medication to make an improvement to thesubject's sleeping disorder based in part on the quantitative analysis.15. The method of claim 14 wherein the measurement time period is lessthan about 15 minutes.
 16. The method of claim 14 wherein themeasurement time period is less than about 10 minutes.
 17. The method ofclaim 14, additionally comprising the step of determining that thesubject has maintained a normal sleeping pattern prior to the analysis.18. The method of claim 14, wherein the subject's EEG is acquired usingat least one dry physiological electrode.
 19. The method of claim 14,wherein the subject's EEG is acquired using only two physiologicalelectrodes, one of two electrodes being a reference electrode.
 20. Themethod of claim 14, wherein at least one of the one or more types ofstimulus provided to the subject during the measurement time period isan auditory stimulus, the auditory stimulus being provided on anintermittent basis, and wherein the subject is instructed to respondafter recognizing one or more of the types of stimulus.